The purpose of this project is to define quantitatively how physical and mechanical parameters in the microcirculation influence and determine whole-organ regulatory and exchange functions. Three major experiments are planned on two organ systems. New innovative techniques developed in the applicant's laboratory will be used. The first experiment is an in vivo study of the mechanisms responsible for pressure induced regional microvascular response gradients in the hamster cheek pouch. A new cheek pouch preparation and an adaptation of the "Wiederhielm box-method" will be used to test the validity of an hypothesis developed by the applicant that explains the origin and basis for vascular response gradients in terms of the length-tension properties of vascular smooth muscle. An in vitro study is also planned on single, isolated arterioles from the cheek pouch using a new state-of-the-art microvessel perfusion system. The purpose of the in vitro study is to obtain a quantitative expression for the relationship between the degree of smooth muscle shortening in "folded" arteriolar walls and changes in "functional internal radius". Exact, quantitative data are presently unavailable and are needed to transpose in vitro microvascular measurements of cell shortening into a quantitative expression for in vivo microvascular resistance changes. The second experimental goal will be to study the origin and mechanisms of the veno-arteriolar reflex response in the microcirculation of rat intestinal muscle, submucosa and mucosal villi. The improved "Wiederhielm box-method" will be employed to identify and compare the myogenic and neurogenic components of the reflex, and to determine how they are modulated in the microcirculation by the initial length-tension states of arterioles and by flow-dependent factors. Parallel studies on single, isolated intestinal arterioles will also be done using the microperfusion system. The third experimental goal will be to measure the hydraulic conductivities (Lp) of single mucosal villus capillaries in the rat intestine. A new "oil-drop" method will be used. The method solves the problem of capillary compliance and allows simultaneous measurement of capillary compliance and fluid flux so that errors in Lp due to compliance are automatically corrected. Measurements of single mucosal fenestrated-capillary Lp's are unavailable at present. The results will provide new insights into our understanding of regional and functional differences in intestinal fluid balance.